Translational research for recurrent lung cancer treatment with combination therapy of gefitinib and meloxicam

吉非替尼联合美洛昔康治疗复发性肺癌的转化研究

• 批准号: 17590808
• 负责人: SATOH Taroh
• 金额: $ 2.09万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17590808/
• 关键词: EGFR; gefitinib; NSCLC; meloxicum; PEG2.; PGI2

It has been said that inhibitor of EGFR, gefitinib is effective for reurrent pretreated Non Small Cell Lung Cancer (NSCLC). Overexpression of COX-II is highly related to prognosis for NSCLC. There are some synergism in anticancer agents and COX-II inhibitors. Expression of COX-II is related to EGFR. Based on these results we conducted phase II clinical trial for NSCLC to investigate effectiveness of combination therapy with gefitinib and COX-II inhibitor, meloxicum.【Objectives】 The objective of this study is to evaluate the response rate and safety of combination therapy with gefitinib and meloxicum.【Patients】 NSCLC patients diagnosed with histology, good performance status(0-2), within 2 regimens of prior treatment and having measurable lesions were eligible for this study.【Methods】 All patients were treated with gefitinib 250mg/meloxicum 10 mg once a day from day 1 until PD.【Results】 Twenty three patients were enrolled. Backgrounds for these patients were as follows; male/female: 10/13、histology; adenocarcinoma/squamous cell carcinoma/NSCLC: 18/3/2、PS (performance status) 0/1/2:3/18/2, clinical stage; III/IV:5/18、MST: 210days. We did not see any correlation in expression level of EGFR. Phosphorelated EGFR, expression of COX-II in histopathopogical staining. There were no relation in plasma level of COX-2, PEG2, PGI2 and other prostagrandines.

EGFR抑制剂吉非替尼（gefitinib）对复发性非小细胞肺癌（non-small Cell Lung Cancer，NSCLC）治疗有效。COX-Ⅱ的过表达与NSCLC的预后密切相关。抗癌药物与COX-Ⅱ抑制剂之间存在一定的协同作用。COX-Ⅱ的表达与EGFR相关。基于这些结果，我们进行了II期临床试验，以研究吉非替尼和COX-II抑制剂美洛昔康联合治疗NSCLC的有效性。[目的]评价吉非替尼与美洛昔康联合治疗慢性乙型肝炎的疗效和安全性。[患者]诊断为组织学、体能状态良好（0-2）、在2种既往治疗方案内且具有可测量病变的NSCLC患者有资格参加本研究。[方法]所有患者均给予吉非替尼250 mg/美洛昔康10 mg，1次/d，第1天开始治疗，直至PD。[结果]共纳入23例患者。这些患者的背景如下：男性/女性：10/13，组织学;腺癌/鳞状细胞癌/NSCLC：18/3/2，PS（体能状态）0/1/2：3/18/2，临床分期; III/IV：5/18，MST：210天。我们没有看到EGFR表达水平的任何相关性。组织病理学染色中磷酸化相关EGFR、COX-Ⅱ表达。血浆考克斯-2、PEG 2、PGI 2及其它甾体类药物浓度与脑梗死发生无相关性。

项目成果

atuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk.

阿图珠单抗和西妥昔单抗可激活表皮生长因子受体，但无法触发 Akt 或 Erk 的下游信号传导。

• 发表时间: 2008
• 期刊: Int J Cancer 122
• 作者: Tsuji T;Aoshiba K;Nagai A.;青柴和徹;青柴和徹;Kazutetsu Aoshiba;Kazutetsu Aoshiba.;Yoshida T;Akashi Y;Yoshida T
• 通讯作者: Yoshida T

Enhancement of the antitumor activity of ionising radiation by nimotuzumab, a humanised monoclonal antibody to the epidermal growth factor receptor, in non-small cell lung cancer cell lines of differing epidermal growth factor receptor status.

• DOI: 10.1038/sj.bjc.6604222
• 发表时间: 2008-02-26
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Akashi, Y.;Okamoto, I.;Iwasa, T.;Yoshida, T.;Suzuki, M.;Hatashita, E.;Yamada, Y.;Satoh, T.;Fukuoka, M.;Ono, K.;Nakagawa, K.
• 通讯作者: Nakagawa, K.

Differential constitutive activation of the epidermal growth factor receptor(EGFR) in non-small cell lung cancer cells bearing EGFR gene mutation and amplification

EGFR基因突变和扩增的非小细胞肺癌细胞中表皮生长因子受体（EGFR）的差异组成型激活

• 发表时间: 2007
• 期刊: Cancer Research 67
• 作者: Tsuji T;Aoshiba K;Nagai A.;青柴和徹;青柴和徹;Kazutetsu Aoshiba;Kazutetsu Aoshiba.;Yoshida T;Akashi Y;Yoshida T;Akashi Y;Yoshida T;Akashi;Okabe T
• 通讯作者: Okabe T

atuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk..

阿图珠单抗和西妥昔单抗可激活表皮生长因子受体，但无法触发 Akt 或 Erk 下游信号传导。

• 发表时间: 2008
• 期刊: Int J Cancer 122
• 作者: Tsuji T;Aoshiba K;Nagai A.;青柴和徹;青柴和徹;Kazutetsu Aoshiba;Kazutetsu Aoshiba.;Yoshida T
• 通讯作者: Yoshida T

atuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk

阿图珠单抗和西妥昔单抗激活表皮生长因子受体，但无法触发 Akt 或 Erk 下游信号传导

• 发表时间: 2008
• 期刊: Int J Cancer 122
• 作者: Tsuji T;Aoshiba K;Nagai A.;青柴和徹;青柴和徹;Kazutetsu Aoshiba;Kazutetsu Aoshiba.;Yoshida T;Akashi Y;Yoshida T;Akashi Y;Yoshida T
• 通讯作者: Yoshida T